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Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma (ALIZE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02814643
Recruitment Status : Completed
First Posted : June 28, 2016
Results First Posted : March 1, 2018
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE June 15, 2016
First Posted Date  ICMJE June 28, 2016
Results First Submitted Date  ICMJE December 12, 2017
Results First Posted Date  ICMJE March 1, 2018
Last Update Posted Date October 24, 2018
Actual Study Start Date  ICMJE July 1, 2016
Actual Primary Completion Date January 24, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2018)
  • Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [ Time Frame: 4 weeks ]
    To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.
  • Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 [ Time Frame: 12 weeks ]
    To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
  • Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 [ Time Frame: 4 weeks ]
    To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
  • Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 [ Time Frame: 12 weeks ]
    To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • Post-dose strain-specific hemagglutination-inhibition (HAI) antibody geometric mean fold rises (GMFRs) [ Time Frame: from week 8 to week 12 ]
    The geometric mean fold rise between the treatments will be assessed with an ANCOVA model on the log-transformed antibody titer fold rise.
  • Post-dose strain-specific serum HAI antibody geometric meant titers (GMTs) [ Time Frame: at week 12 ]
    The geometric mean titers between the treatments will be assessed with an ANCOVA model on the log-transformed antibody titer.
  • Proportion of patients who experience a strain-specific post-dose antibody response with antibody response defined as a ≥4-fold rise in HAI antibody titer [ Time Frame: from week 8 to week 12 ]
  • Proportion of patients who achieve a strain-specific post-dose HAI antibody titer ≥40 [ Time Frame: at week 12 ]
Change History Complete list of historical versions of study NCT02814643 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2018)
  • Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 [ Time Frame: 12 weeks ]
    To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
  • Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [ Time Frame: 4 weeks ]
    To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.
  • Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 [ Time Frame: 12 weeks ]
    To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
  • Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 [ Time Frame: 4 weeks ]
    To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
  • Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 [ Time Frame: 12 weeks ]
    To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • Proportion of patients who achieve a strain-specific post-dose HAI antibody titer ≥320 [ Time Frame: at week 12 ]
  • Post-dose strain-specific microneutralization (MN) antibody GMFRs [ Time Frame: from week 8 to week 12 ]
  • Post-dose strain-specific serum MN GMTs obtained [ Time Frame: at week 12 ]
  • Proportion of patients who experience a strain-specific post-dose antibody response with antibody response defined as a ≥4-fold rise in MN antibody titer [ Time Frame: from week 8 to week 12 ]
  • Change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score [ Time Frame: at week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: June 23, 2016)
  • Adverse events [ Time Frame: weeks 0 to 20 ]
  • Serious adverse events [ Time Frame: weeks 0 to 20 ]
  • Laboratory variables for safety and tolerability of benralizumab [ Time Frame: weeks 0 to 20 ]
    Laboratory variables in Serum chemistry, Hematology and Urinalysis
  • Physical Examination [ Time Frame: weeks 0 to 20 ]
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma.
Brief Summary This is a randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of a fixed dose of benralizumab administered subcutaneously (SC) on antibody responses following seasonal influenza virus vaccination
Detailed Description This study is designed to investigate the potential effect of benralizumab on the antibody response to the seasonal influenza virus vaccine in patients 12-21 years of age with asthma. Benralizumab will be given subcutaneously (SC) at Weeks 0, 4, and 8 weeks, at which time benralizumab levels will reach steady state. Patients will then receive 1 dose of intramuscular (IM) seasonal influenza virus vaccine at Week 8 and samples drawn at Week 8 and Week 12 to measure the antibody response to the influenza virus
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Benralizumab
    Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
  • Drug: Benralizumab Placebo
    Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
  • Drug: Seasonal influenza virus vaccine
    Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Study Arms  ICMJE
  • Experimental: Benralizumab
    1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
    Interventions:
    • Drug: Benralizumab
    • Drug: Seasonal influenza virus vaccine
  • Placebo Comparator: Placebo
    1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
    Interventions:
    • Drug: Benralizumab Placebo
    • Drug: Seasonal influenza virus vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2018)
103
Original Estimated Enrollment  ICMJE
 (submitted: June 23, 2016)
100
Actual Study Completion Date  ICMJE January 24, 2017
Actual Primary Completion Date January 24, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female and male patients aged 12 to 21 years, inclusive, at the time of Visit 1
  • Weight of ≥40 kg
  • Documented history of current treatment with Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA)
  • Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >50% predicted at Visit 1 or Visit 2.
  • Airway reversibility (FEV1 >12% and 200 ml) demonstrated at Visit 1 or Visit 2 using the Maximum Post-bronchodilator Procedure OR
  • Airway reversibility documented in the previous 12 months prior to Visit 1
  • An exacerbation, 1 or more, that required oral corticosteroids in the previous year OR
  • Any condition assessed by patient recall over the previous 2-4 weeks

Exclusion Criteria:

  • Clinically important pulmonary disease other than asthma
  • Known history of allergy or reaction to the Investigational Product formulation or influenza vaccine
  • Receipt of an influenza vaccine within 90 days prior to randomization
  • Poorly controlled asthma during the screening period that requires treatment with oral corticosteroids or a hospitalization/emergency room visit for the treatment of asthma
  • Acute illness or evidence of significant active infection or known influenza infection during the current flu season
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02814643
Other Study ID Numbers  ICMJE D3250C00033
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pamela L Zeitlin, M.D. Ph.D. Johns Hopkins University
PRS Account AstraZeneca
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP